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Cardiac Toxicity 4 to 20 Years After Completing Anthracycline Therapy

Laurel J. Steinherz, MD; Peter G. Steinherz, MD; Charlotte T. C. Tan, MD; Glenn Heller, PhD; M. Lois Murphy, MD
JAMA. 1991;266(12):1672-1677. doi:10.1001/jama.1991.03470120074036.
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Objective.  —To assess the cardiac status of long-term survivors of pediatric malignancies who received chemotherapy, including anthracyclines.

Design and Method.  —Patients were evaluated by echocardiogram from 4 to 20 years (median, 7 years) after completion of anthracyclines, with prospective and retrospective analysis.

Patients.  —The consecutive sample of 201 patients had received a total anthracycline dose of 200 to 1275 mg/m2 (median, 450 mg/m2), and 51 patients had mediastinal radiotherapy.

Main Outcome Measures.  —The overall incidence and severity of abnormal systolic cardiac function were determined for the entire cohort. Risk factors of total anthracycline dose, mediastinal radiotherapy, age during treatment, and length of follow-up were examined.

Results.  —Twenty-three percent (47/201) of the cohort had abnormal cardiac function on noninvasive testing at long-term follow-up. Correlation between total cumulative dose, length of follow-up, and mediastinal irradiation with incidence of abnormalities was significant. Fifty-six patients were followed up for 10 years or more (median, 12 years), with a median anthracycline dose of 495 mg/m2, Thirty-eight percent (21/56) of these patients, compared with 18% (26/145) of patients evaluated after less than 10 years, had abnormal findings. Sixty-three percent of patients followed up for 10 years or more after receiving 500 mg/m2 or more of anthracyclines had abnormal findings. Nine of 201 patients had late symptoms, including cardiac failure and dysrhythmia, and three patients died suddenly. Microscopic examination of the myocardium on biopsy and autopsy revealed fibrosis.

Conclusion.  —The 23% incidence of late cardiac abnormalities warrants continued evaluation of patients after anthracyclines to guide patient care and the design of future chemotherapeutic protocols.(JAMA. 1991;266:1672-1677)


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